Pharmacogenomics Validation for Imatinib in Chronic Myeloid Leukemia

NCT01437202 | Completed

• 1 other identifier: AMC-H-64
• Study Type: observational
• Target: 100
• Locations: 2 countries
• Sites: 3

Brief Summary

This is a multicenter, retrospective, observational study to validate a pharmacogenetics model for imatinib metabolism and resistance in patients with chronic myeloid leukemia among patients in different independent cohort.

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Keywords

imatinib; drug resistance; pharmacogenetics

Outcome Measures

Primary Outcomes (1)

• Median time to CCyR (complete cytogenetic response)

  Difference of median time to CCyR between cohorts according to the risk stratification by gene analysis

Secondary Outcomes (2)

• Variance of Genotypes from CML patients with Korean ethnicity

• Median time to MCyR (Major cytogenetic responses)

Study Arms (3)

high risk group

Identified by the predictive model using 2 genotypes and disease stage

intermediate risk group

Identified by the predictive model using 2 genotypes and disease stage

Low risk group

Identified by the predictive model using 2 genotypes and disease stage

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients who were diagnosed as chronic myeloid leukemia, treated with imatinib more than 3 months, at Asan Medical Center, Seoul, Korea.

You may qualify if:

• Chronic myeloid leukemia of any stage including chronic phase, accelerated or blastic phase.
• Age\>18 years
• Complete set of clinical data available for review (demographic data, stage, treatment history, cytogenetic reports, and latest BCR/ABL RQ-PCR results)
• Treated with imatinib mesylate at least 3 months

You may not qualify if:

• Treated with imatinib mesylate less than 3 months
• Not agree with the intention of this study

Sponsors & Collaborators

• Asan Medical Center: lead

Study Sites (3)

Princess Margaret Hospital, University of Toronto

Toronto, Canada

Location

Asan Medical Center, University of Ulsan College of Medicine

Seoul, South Korea

Location

Samsung Medical Center, Sungkyunkwan University School of Medicine

Seoul, South Korea

Location

Related Publications (7)

• Kantarjian HM, Cortes JE, O'Brien S, Luthra R, Giles F, Verstovsek S, Faderl S, Thomas D, Garcia-Manero G, Rios MB, Shan J, Jones D, Talpaz M. Long-term survival benefit and improved complete cytogenetic and molecular response rates with imatinib mesylate in Philadelphia chromosome-positive chronic-phase chronic myeloid leukemia after failure of interferon-alpha. Blood. 2004 Oct 1;104(7):1979-88. doi: 10.1182/blood-2004-02-0711. Epub 2004 Jun 15.

  PMID: 15198956 BACKGROUND

• Kantarjian HM, Talpaz M, Giles F, O'Brien S, Cortes J. New insights into the pathophysiology of chronic myeloid leukemia and imatinib resistance. Ann Intern Med. 2006 Dec 19;145(12):913-23. doi: 10.7326/0003-4819-145-12-200612190-00008.

  PMID: 17179059 BACKGROUND

• Gorre ME, Mohammed M, Ellwood K, Hsu N, Paquette R, Rao PN, Sawyers CL. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science. 2001 Aug 3;293(5531):876-80. doi: 10.1126/science.1062538. Epub 2001 Jun 21.

  PMID: 11423618 BACKGROUND

• Mahon FX, Belloc F, Lagarde V, Chollet C, Moreau-Gaudry F, Reiffers J, Goldman JM, Melo JV. MDR1 gene overexpression confers resistance to imatinib mesylate in leukemia cell line models. Blood. 2003 Mar 15;101(6):2368-73. doi: 10.1182/blood.V101.6.2368.

  PMID: 12609962 BACKGROUND

• Awidi A, Salem II, Najib N, Mefleh R, Tarawneh B. Determination of imatinib plasma levels in patients with chronic myeloid leukemia by high performance liquid chromatography-ultraviolet detection and liquid chromatography-tandem mass spectrometry: methods' comparison. Leuk Res. 2010 Jun;34(6):714-7. doi: 10.1016/j.leukres.2009.08.005. Epub 2009 Sep 9.

  PMID: 19744707 BACKGROUND

• Gardner ER, Burger H, van Schaik RH, van Oosterom AT, de Bruijn EA, Guetens G, Prenen H, de Jong FA, Baker SD, Bates SE, Figg WD, Verweij J, Sparreboom A, Nooter K. Association of enzyme and transporter genotypes with the pharmacokinetics of imatinib. Clin Pharmacol Ther. 2006 Aug;80(2):192-201. doi: 10.1016/j.clpt.2006.05.003.

  PMID: 16890580 BACKGROUND

• Kim DH, Sriharsha L, Xu W, Kamel-Reid S, Liu X, Siminovitch K, Messner HA, Lipton JH. Clinical relevance of a pharmacogenetic approach using multiple candidate genes to predict response and resistance to imatinib therapy in chronic myeloid leukemia. Clin Cancer Res. 2009 Jul 15;15(14):4750-8. doi: 10.1158/1078-0432.CCR-09-0145. Epub 2009 Jul 7.

  PMID: 19584153 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

whole blood 4cc

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jong Won Kim, MD, PhD

  Samsung Medical Center, Sungjyunkwan University School of Medicine, Seoul, Korea

  STUDY CHAIR

• Dae-Young Kim, MD

  Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: September 19, 2011
• First Posted: September 20, 2011
• Study Start: September 1, 2011
• Primary Completion: September 1, 2012
• Study Completion: October 1, 2012
• Last Updated: July 9, 2014

Record last verified: 2014-07

Locations

KR (2); CA (1)